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It’s enough to make a doctor’s head ache—antithrombotic drugs may protect people from stroke or heart attack, but the same medications may also increase risk of cerebral microbleeds. A study in the June issue of the Archives of Neurology indicates that use of the anti-platelet aggregation drugs aspirin and carbasalate calcium is associated with a higher risk for microbleeds in elderly people. These tiny hemorrhages have been linked with cerebral amyloid angiopathy, a condition in which β amyloid forms vascular deposits, and Alzheimer disease. The research, led by principal investigator Monique Breteler, first author Meike Vernooij, and colleagues at the Erasmus MC University Medical Center in Rotterdam, The Netherlands, does little to ease the pain, however, as more research will be necessary to help doctors accurately weigh the risks and benefits of such therapies.

“We think of aspirin or anti-platelet treatments as being completely safe, but we know that’s not true,” said Steven Greenberg of Harvard Medical School in Boston, who was not involved in the current study. Although the positive effects of aspirin usually outweigh the worry that it will cause bleeding in the stomach or elsewhere, he said, doctors must always consider the risk.

The study, part of a longitudinal study of elderly volunteers in Rotterdam, focuses attention on cerebral microbleeds, which can be disease-related or asymptomatic. “They may, in fact, be a precursor to intercerebral hemorrhage,” said Jack de la Torre of the Sun Health Research Institute in Sun City, Arizona, who was also not part of the study. Microbleeds are more common in older people, he said.

In a cross-sectional analysis, the authors surveyed 1,062 people who participated in the Rotterdam study and had undergone MRI, which allows visualization of microbleeds. They collected pharmacy data to determine who was taking anticoagulants such as heparin or vitamin K agonists, or the platelet aggregation inhibitors aspirin or carbasalate calcium, which both include the active ingredient salicylate. They also collected data on cardiovascular disease, which could confound their results, and adjusted their analysis accordingly. The 245 people who used salicylate drugs had more microbleeds than the people who did not. Use of anticoagulants did not change the rate of microbleeds.

The researchers found differences in the location of microbleeds between the 67 people who used only aspirin and the 141 who took solely carbasalate calcium. Aspirin was linked to lobar bleeds, while carbasylate calcium users were more likely to exhibit infarcts or white matter lesions. “As far as the chemistry is concerned, it really doesn’t make that much sense,” de la Torre said, since both medications work via salicylate. He noted that the active dose of salicylate in carbasalate calcium is generally less than in aspirin, so dosage might explain the differences.

As the authors point out, the study is limited by its cross-sectional nature and cannot suggest cause and effect. “The people who get aspirin or anticoagulants are different from the people who don’t,” Greenberg said. “They controlled for that in as many ways as possible, but still, it’s hard to consider the question as really settled.” The study size is also relatively small, de la Torre noted: “When you consider the complexity of the microbleeds and what surrounds this phenomenon, 67 patients may not be enough to make firm conclusions.” The research does suggest, however, that a larger study may be warranted.

“The point everybody wants to know, Is this something that should make us worry about use of anti-platelet drugs?” Greenberg said. “The answer is a resounding, ‘Not yet.’ At this point, I don’t think there is any cause for worry.”—Amber Dance